The overall objectives of this grant application are: 1. To use gas chromatography-mass spectrometry to define the biliary bile acid composition and characterize unusual bile acids in gallstone patients at the Mayo Clinic, participating in two treatment programs including the National cooperative Gallstone Study, before and after treatment with chenodeoxycholic acid. This study will employ capillary gas chromatography to achieve high resolution separations of bile acids prior to mass spectrometry, and will be coupled with chemical ionization techniques recently developed for bile acid identification. To use gas chromatography-mass spectrometry-accelerating voltage alternation to determine plasma and liver concentrations of lithocholic acid in these patients, by an inverse isotope dilution procedure employing deuterium labeled lithocholic acid. These measurements will be correlated with liver morphology studies by light and electron microscopy. To develop and validate a dual isotope, single sampling technique, based upon deuterium and carbon-13 labeled bile acids which will permit both bile acid pool size and synthesis rate to be determined from a single sampling of the bile acid pool, after labeling with stable isotopes.